Department of Psychiatry, University of Bonn, Bonn, Germany.
J Alzheimers Dis. 2010;22(2):459-68. doi: 10.3233/JAD-2010-100561.
In Alzheimer's disease (AD), the cerebral pathological changes begin many years before the clinical manifestation of the disease. Biomarkers for AD, such as the cerebrospinal fluid (CSF) concentrations of amyloid-β1-42 (Aβ1-42) and tau phosphorylated at threonine 181 (pTau181), may reflect these cerebral changes relatively early. Accordingly, cognitively healthy subjects at risk for AD often have altered CSF concentrations of Aβ1-42 and pTau181. In this study, we assessed the effects and interaction of two strong risk factors for AD, aging and the presence of the APOEε4 allele, on the CSF Aβ1-42 and pTau181 concentrations in 280 adults with normal cognition across the lifespan. For comparison, we further included 152 patients with probable AD. We found significant effects of age on the CSF Aβ1-42 and pTau181, and of the APOEε4 genotype on the Aβ1-42 levels in the cognitively normal participants. Carrying the APOEε4 allele was associated with a significant decrease of the Aβ1-42 concentrations in middle-aged and older participants. In the group of participants with AD, the Aβ1-42 levels were significantly lower in the APOEε4 carriers compared to the non-carriers. These findings demonstrate significant age effects on the CSF Aβ1-42 and pTau181 across lifespan. They also suggest that the decrease of Aβ1-42, but not the increase of pTau181 CSF levels is accelerated by the APOEε4 genotype in middle-aged and older adults with normal cognition.
在阿尔茨海默病（AD）中，大脑的病理变化早在疾病的临床表现出现之前就已经开始了。AD 的生物标志物，如脑脊液（CSF）中淀粉样蛋白-β1-42（Aβ1-42）和磷酸化的苏氨酸 181 处的 tau（pTau181）的浓度，可能相对较早地反映这些大脑变化。因此，有 AD 风险的认知健康受试者通常会改变 CSF 中 Aβ1-42 和 pTau181 的浓度。在这项研究中，我们评估了 AD 的两个强风险因素，即衰老和 APOEε4 等位基因的存在，对 280 名认知正常的成年人整个生命周期中的 CSF Aβ1-42 和 pTau181 浓度的影响和相互作用。为了比较，我们还进一步纳入了 152 名可能患有 AD 的患者。我们发现年龄对 CSF Aβ1-42 和 pTau181 有显著影响，APOEε4 基因型对认知正常参与者的 Aβ1-42 水平有显著影响。携带 APOEε4 等位基因与中年和老年参与者的 Aβ1-42 浓度显著降低有关。在 AD 患者组中，与非携带者相比，APOEε4 携带者的 Aβ1-42 水平显著降低。这些发现表明，在整个生命周期中，年龄对 CSF Aβ1-42 和 pTau181 有显著影响。它们还表明，APOEε4 基因型在中年和老年认知正常个体中加速了 Aβ1-42 的减少，而不是 pTau181 CSF 水平的增加。
